Normal functioning of te nervous system depends upon the formation of vast numbers of specific connections between neurons. The mechanisms involved in producing this specificity are unknown, and their discovery presents the outstanding quest in developmental nuerobiology. One profitable approach is the use of genetics: the molecular basis of this specificity may be arrived at through the analysis of mutations which disrupt proper connectivity. Such mutations may alter genetic factors directly involved in neural development. For instance, if surface-bound molecules are mediating the specificity of neural connections, then genes coding for either the molecules themselves or enzymes involved in their synthesis might be identified. However, before genetics can be used rationally as a tool to probe for answers on the molecular level, the effects of mutations on neuronal connectivity must be investigated on the cellular level. We hae isolated several mutations in Drosophila melanogaster which disrupt normal connectivity in the nervous system. The most exciting of thse alters a gene which we believe is directly involved in establishing proper connectivity between two identified neurons of the giant fiber system. This mutation, bendless, deletes the specific branch of the giant fiber which normally makes synaptic contact with the motorneuron to the jump muscle. Our goal in the next several years is to elucidate the role of this gene during development in establishing the proper connectivity between the giant fiber and jump motoneuron. 1. By using normarski optics and lucifer yellow fills we will determine at what time and in what manner mutant giant fibers deviate from the normal developmental sequence. 2. We will isolate new alleles of the bendless gene (especially extreme and temperature sensitive alleles). 3. By the use of mosaics we will determine what cells must have mutant genotype in order for the bendless phenotype to be expressed.